We hypothesize that the analytical and clinical validation of cardiac troponin (cTnl) and cardiac troponin T (cTnT) will enable the establishment of reference ranges in a healthy population to be used as cutoff levels for the sensitive and specific detection of acute myocardial infarction (AMI), supporting the replacement of creatine kinase MB (CKMB) as the new standard biochemical marker for AMI. Further, validation of the major diagnostic manufacturer's troponin assays will enable cardiac troponins to be used to assist in risk stratifying acute coronary syndrome patients. We plan to analytically validate the precision of the leading diagnostic manufactures instruments which market cTnl, cTnT and CKMB assays. Reference ranges will be established for each assay by race, sex, and age in both plasma and serum. Clinical performance of each assay (defined by ROC curve analyses) will be assessed using each cardiac maker assay for detection of AMI, compared to the ICD-9-CM classification codes used at Hennepin County Medical Center for 1000 to 1500 consecutive acute coronary syndrome (myocardial ischemia) admissions, of which 200 to 300 will have AMI. Modified WHO diagnostic criteria for AMI (endorsed by the ACC, ESC, and AHA) that uses cardiac troponin results from each manufacturers' assay will be compared to CKMB results. Clinical performance of each cardiac marker assay (using logistic multiple regression analysis) will also be assessed for its ability to assess cardiac events (AMI, cardiac related death) during hospitalization and 30 days following admission in both ST segment elevation (n=100 to 200) and non-ST segment elevation (n=100 to 200) AMI patients compared to unstable angina patients (150 to 300). The findings of this proposal will support the standards of laboratory medicine practice guidelines as well as the consensus document of the joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction addressing the need to support cardiac troponin testing as the definitive marker for detection of myocardial damage, AMI, and for risk stratification in the 6 million patients that present annually to hospitals with signs and symptoms of AMI.